What Most People Don’t Know About Mutations

_{Jonathan Bartlett

April 12, 2021

Intelligent Design}

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One thing that I’ve found interesting is how ignorant many people – even many biologists! – are about the mutational processes in the cell. The idea that mutations come from copying “errors” is so embedded in our collective consciousness, that it is hard to get people to even fathom alternatives.

Thinking of mutation as a biological process – one under the organization/direction of the cell – leads to a lot of interesting biology. There are indeed copying errors, but my guess is that by the end of the century we will find that the ones that are actually errors are by far the least numerous. This is like the discovery of microbes. We first found them *because* they caused disease. Therefore, our first reaction was that microbes *are* diseased. But later we find out that >99% of them are actually good for us and the environment, and there are just a handful that are problematic.

Normally, DNA is copied by DNA Polymerase III. Yes, there are more than one DNA polymerase gene! Why, you ask? That’s because DNA Polymerase III is a “high-fidelity” polymerase, basically making exact copies. But, if the cell detects that it *needs* mutations, it switches to a SEPARATE GENE, whose function is to copy DNA *while inserting* mutations!

So, in E. coli, the “SOS response” system is well-studied. In this system, when E. coli is stressed (lack of food, etc.), it tries to alter its own physiology by inducing mutations. It switches from the high-fidelity DNA Polymerase III to one of the other polymerases (II, IV, or V), which induce various mutations. It also makes lots of copies of its metabolism genes using these polymerases, since these are the genes most likely to confer benefit from mutating if the organism is starving.

Then, when a mutation is found that relieves the stress, it turns off the mutation-inducing polymerase, and goes back to DNA Polymerase III to get high-fidelity copies of the new gene.

So, as you can see, the Darwinian view of “random mutations” is simply false. The organism has SEPARATE genes for creating mutations, and invokes them when it has need of mutations, and focuses mutations on the genes that are likely to yield benefits.

Comments

Reading back over the paper, I think you are correct (at least in their model - later authors have disagreed about whether their model actually describes the biology). The model they are pushing has the amplification as a mutant phenotype first, and then an increased mutation rate. This model would not match the scenario I describe for directed mutations. I think when I read this years ago in concert with other papers which described the same general idea but with other models, and read it with those models in mind and read it into the paper. Thanks for the correction! johnnyb

But there is no choice in these experiments orthomyxo

The Hendrickson paper was to highlight the choice of genes to amplify as a part of the process. I don't think Hendrickson thought this was important, but I certainly do. johnnyb

My point is that a non-directed mutation would have no reason to be more likely to benefit the organism
Then the Hendrickson paper would not be directed mutation, though? The lac genes are not targeted for duplication, they will just duplicate in one or a few cells and then be subject to selection. All the other genes will have duplicates also (given a big enough population or a enough time). orthomyxo

OK, thanks. That makes things clearer. So just a change in mutation rate isn't directed. Bob O'H

I've punted? I thought I answered pretty straightforwardly @15. I'll give it another try and you can tell me if I'm clearer. A non-directed mutation is one that is "accidental". Essentially, it has no better chance of hitting a beneficial configuration than if the mutation had occurred at random. Note that I'm not saying that mutations occur in a uniformly distributed randomness. My point is that a non-directed mutation would have no reason to be more likely to benefit the organism than one that is drawn at random. A directed mutation, therefore, is one whose mutation mechanism *does* make it more likely to give benefit to the organism than one drawn at random. johnnyb

johnnyb - it's impossible to discuss this with you, as I've asked you twice what you mean by directed, and twice you've punted. In your new post you point out that changes in mutation rate are more complex, but still make no comment a bout what is or in not directed. How can you write so much about "directed mutations" if you are unwilling to say what they are? Bob O'H

Also - anyone coming back to this - I also have a new thread on measuring the phenomena of (3). Measuring the Directedness of Mutations johnnyb

Mung - I'll post something like that later this week or next. I have another post I want to work with first. johnnyb

Bob - The authors of the paper are under the same faulty paradigm you are under. But the mechanics exactly match what I said. In fact, just to point out to Viola that my terminology is not outdated, the authors of this paper specifically talk about "neo-Darwinism". The problem is that they do not consider category (3), and assume that anything not in category (4) is in category (2). The fact that they have supplied specific evidence to category (3) and not recognize it is literally the problem I'm pointing out. Now, they do argue against the role of mutating DNA, but this is shown in a later paper to be wrong (see A Switch from High-Fidelity to Error-Prone DNA Double-Strand Break Repair Underlies Stress-Induced Mutation). My point about the paper was to validate the point that the mutations are caused by increased transcription, which is based on the needs of the organism - the organism is increasing transcription of a gene it needs mutation of. johnnyb

The terms “Darwinian” or “Darwinist” are employed by proponents of intelligent design and/or creationism as a pejorative epithet for any metaphysical, ideological, theological or scientific perspective which is held to be inimical to their own religious presuppositions.
The term “Darwinism” is how many if not most evolutionary biologists describe themselves. https://plato.stanford.edu/entries/darwinism/
Darwinism designates a distinctive form of evolutionary explanation for the history and diversity of life on earth. Its original formulation is provided in the first edition of On the Origin of Species in 1859. This entry first formulates ‘Darwin’s Darwinism’ in terms of five philosophically distinctive themes: (i) probability and chance, (ii) the nature, power and scope of selection, (iii) adaptation and teleology, (iv) nominalism vs. essentialism about species and (v) the tempo and mode of evolutionary change. Both Darwin and his critics recognized that his approach to evolution was distinctive on each of these topics, and it remains true that, though Darwinism has developed in many ways unforeseen by Darwin, its proponents and critics continue to differentiate it from other approaches in evolutionary biology by focusing on these themes. This point is illustrated in the second half of the entry by looking at current debates in the philosophy of evolutionary biology on these five themes.
Yes, some ID proponents use the term pejoratively because of the hypocrisy of those who use Darwin’s ideas as currently understood to underpin a specious theory of evolution. What would you call someone who backs a bogus theory of science. The best word is hypocrite. Darwinist is actually a kinder designation. Question: what would you call blind acceptance to a false worldview (Darwinism?) Might religious be a proper descriptive? Especially when many of its adherents claim theological implications for this bogus worldview. jerry

The best-adapted individuals leave behind more offspring than less well-adapted individuals. Given enough time, one species may evolve into many others. There is no research that contradicts ID’s assessment.
The key phrase is “may evolve into many others.” ID doesn’t deny this “maybe” but says it is so rare and so trivial that it explains little if anything of interest in evolution. Two of the most famous evolutionary scientists, Rosemary and Peter Grant, said it takes over 20 million years to form one new bird species. And there is nothing essentially new after this time.
I’m pretty sure there are quite a lot of additional complexity and factors that contribute to genetic changes in populations of organisms.
Yes, there are. I refer to them above. However, none of them have led to any changes in life forms that build anything new of consequence. If there were any, the critics of ID would be all over this site, with the examples. But they are as silent as the dog barking in the night. Speculation is the main evidence of macro evolutionary biology. jerry

F/N: Monod as a key case in point of evolutionary materialistic scientism: https://uncommondescent.com/atheism/monods-objectivity-naturalistic-scientism-and-begging-big-questions/ KF kairosfocus

F/N: it is appropriate to ponder just how random and just how randomising mutations are. Also, just how much information can be created through chance variations incrementally filtered for differential reproductive success, in relevant time scales.Especially, as most such variations, arguably, will be deleterious or may break down existing information. KF kairosfocus

Seversky, kindly read the UD correctives, here: https://uncommondescent.com/faq/#drwnterm You are taking needless offence to play the verbal intimidation game that is all too common now as a substitute for reasoned discussion. Modern Evolutionary theorising predominantly traces to Darwin and to the Neo-Darwinian synthesis, so it is not unreasonable to speak in light of that pattern. That, in a context where you have had to be repeatedly corrected for the loaded conflation "intelligent design creationists." Well do you know that an apt short descriptive summary of a major ideological movement in modern thought is evolutionary materialistic scientism [often termed, naturalism], with fellow travellers. KF kairosfocus

Johnnyb @ 15 - first, can you answer my question "What do you mean by “directed”?". Do you just mean changing the rate of mutation?
Specifically, when the SOS system is turned on due to lack of food, the genes that are amplified mutagenically are specifically those involved in external metabolism. For evidence, here’s a paper for you: Amplification–mutagenesis: Evidence that “directed” adaptive mutation and general hypermutability result from growth with a selected gene amplification
What? You mean the paper that argues exactly the opposite:
Selective stress has no direct effect on mutation rate or target specificity, but acts to favor a succession of cell types with progressively improved growth on lactose.
Their argument is that there is strong selection for increasing the copy number of the mutant lac gene, because it has some function so amplification increases the amount of function. Bob O'H

The terms "Darwinian" or "Darwinist" are employed by proponents of intelligent design and/or creationism as a pejorative epithet for any metaphysical, ideological, theological or scientific perspective which is held to be inimical to their own religious presuppositions. Ever since science was able to distance itself from religious influence it has had to be on its guard against being 'brought back into the fold' and risking subjection to some sort of religious "Lysenkoism". It's true that science does not operate in a metaphysical vacuum and the assumptive metaphysics matter, which means that science should not be judged on the grounds of its conformity to a particular theology or political ideology but by simply by whether it works. The theories of relativity and quantum mechanics are two of the strongest in science. They have been verified by extensive observation and experiment to extremely high degrees of accuracy. Yet they are incomplete. There is great difficulty in trying to reconcile the two and science may have to await a newer and greater theory which can supersede both of them. The value of that theory should not be determined by its acceptability to Christians or Muslims, conservatives or liberals, socialists or capitalists, even though many in those groups would dearly love to have that power. Seversky

Thanks, Johnny. That's pretty basic. Although I don't know much, I'm pretty sure there are quite a lot of additional complexity and factors that contribute to genetic changes in populations of organisms. But I really have other interests, so I'll leave this topic at that. Viola Lee

Perhaps JB would be so kind as to create a new topic here at UD on the subject of "Common Design." Mung

By the way, Viola, here is the NIH and how they *presently describe* evolution. It's straight out of the modern synthesis.
Evolution is the process by which organisms change over time. Mutations produce genetic variation in populations, and the environment interacts with this variation to select those individuals best adapted to their surroundings. The best-adapted individuals leave behind more offspring than less well-adapted individuals. Given enough time, one species may evolve into many others.
johnnyb

Thanks UB! johnnyb

. Enjoying your paper, JB. A nice read. Upright BiPed

Viola - I agree with what Jerry has said. In addition, there has been an "Extended Synthesis" proposed, but (a) it is highly controversial, and (b) even though it is controversial, its proponents have tried to water it down as much as possible to get it to be the standard. I tried to give it some specificity in the paper below, but haven't had much success getting others to adopt it. Evolutionary Teleonomy as a Unifying Principle for the Extended Evolutionary Synthesis Of particular note is the section "How Evolutionary Teleonomy Aids Biological Reasoning," where I show a specific example in the current literature where the modern synthesis is causing inappropriate combinations of data sets. johnnyb

"What do you mean by “directed”? If you mean that the mutation rate is increased, then OK but “directed” seems to be a mis-nomer." Okay, there is a HUGE scale here, going from: (1) no direction of mutation in time or space (2) direction of mutation in time but not space (3) direction of mutation in time and partial space (4) direction of mutation in time and specific space It actually lands on (3). Now, there are ORDERS OF MAGNITUDE difference between (1) and (2), and your description of it seems to imply (2). I'm arguing for (3) in this case, which is also orders of magnitude more specific than (2). Specifically, when the SOS system is turned on due to lack of food, the genes that are amplified mutagenically are specifically those involved in external metabolism. For evidence, here's a paper for you: Amplification–mutagenesis: Evidence that “directed” adaptive mutation and general hypermutability result from growth with a selected gene amplification So, as I've stated, when the cell needs mutations, it turns on its mutator polymerases, and then copies the genes that it likely needs changes in. Now, there *are* instance of (4) (see, for instance, "Transposable Elements as Activators of Cryptic Genes in E. coli"), but I would argue that (3) is a much more widespread behavior. johnnyb

The “replication errors” is a subjective judgement. Is it a “modification” or an “error” if it is directed? What if it is only partially directed (i.e., part of a set of possibilities, but with some indeterminacy)?
What do you mean by "directed"? If you mean that the mutation rate is increased, then OK but "directed" seems to be a mis-nomer. If you mean that the cell uses these polymerases to induce particular mutations, then what evidence do you have? Bob O'H

Hasn’t the scientific understanding of factors involved with evolution changed quite a bit since then?
Yes and no. We had this discussion before when you asked about HGT. The modern synthesis as a term was first used about 100 years ago but essentially remains the same and now in 2021 is sometimes called something different. It now obviously includes DNA etc. But the thinking is almost the same today. Variation filtered through natural selection leads to change. The sources of variation are numerous. In the hundreds. Nothing controversial about that. It’s just the actual results from this process that are under dispute. Most scientists will agree with the proposition that all or most changes in life forms since the first life forms appeared happened this way. ID says there is no evidence for such an understanding. But despite this lack of proof, the ruling paradigm is that it happened this way. And objecting to it leads to censure. Not much different from a lot of philosophical worldviews throughout history. jerry

Hi Johnny. You write, "It sounds like you think that all scientists agree about everything, are up-to-speed about everything, and that information immediately flows from what’s happening in the labs to what other scientists know and teach. " Hmmm. I don't think that at all, and don't know why what I wrote makes you think I do. Anyway, I googled "modern synthesis", and Wikipedia calls it an early 20th century synthesis, which makes it about 100 years old. Hasn't the scientific understanding of factors involved with evolution changed quite a bit since then? Viola Lee

Natural selection is based around subjective terminology, differential reproductive "success", which subjective terminology is then objectified. The entire life cycle of organisms is explained using all kinds of subjective words, in regards to this success. That is why Darwinism is materialist ideology, because subjective terminology is the language of ideology. "and as natural selection works solely by and for the good of each being all corporeal and mental endowments will tend to progress towards perfection" C. Darwin, Origin Of Species See, it is ideology. It should read " as natural selection works solely by and for the reproduction of each being, all corporeal endowments will tend to be shaped towards optimal contribution to reproduction." That would be non ideological. This error in natural selection theory is caused by an uncertainty in the theory to describe in terms of competition, or reproduction. It is wanting to say too many things at the same time. It ends up presenting an arbitrary focus on competition. This error leads to wrong conclusions in scenario's where competition is irrelevant. Like for instance with combatting infectious diseases. It is not really the point that variant A competes with variant B, the point then is for it to reproduce at all. As like with endangered species, the point is for it to reproduce at all. Also in radiating out, taking new oppurtunities, competition is largely irrellevant. Also the mental endowments should be left out, because it is too vague a term. A mental endowment such as personal character, is not material or heritable, because it is subjective. And it is a very grave error to confuse what is subjective with what is objective. The other way Darwinism is ideology, is that it is held in opposition to creationism / intelligent design. Unlike Darwinism, Creationism does properly separate subjectivity from objectivity, with it's 2 separate categories of creator and creation. So in it's denial of creationism, Darwinist use of subjective words, becomes s to be a replacement for the proper subjectivity of creationism. When you say, oh but I use the words "beneficial" mutations, reproductive "success" etc. in a technical sense, apart from other uses of these words as subjective, that shit does not fly when you go out of your way to destroy the properly subjective creationist use of these words. You see subjectivity is an inherently creationist concept. mohammadnursyamsu

Bob - The "replication errors" is a subjective judgement. Is it a "modification" or an "error" if it is directed? What if it is only partially directed (i.e., part of a set of possibilities, but with some indeterminacy)? A good review is "Environmental Stress and Lesion-Bypass DNA Polymerases". The first part is more on the "lesion bypass" side, but in the later part of the article it talks about how these same polymerases are involved in relieving environmental stresses in stationary phase E. coli. As for Pol II, I included it primarily just because it is part of the SOS response. However, there is some evidence of it being a beneficial frameshifter. The article I linked to links to articles about this and provides additional references. johnnyb

The Darwinian ideological mindset implies materialism. That mindset dispenses with telic processes. That mindset says that blind and mindless processes produced sight and consciousness. ET

Viola - "Was it not scientists who discovered all this, and thus broadened our knowledge about how genetics works?" Yes! Who said it wasn't? It sounds like you think that all scientists agree about everything, are up-to-speed about everything, and that information immediately flows from what's happening in the labs to what other scientists know and teach. Darwinism refers to the "modern synthesis" - the idea that the primary driver of evolution is random mutation filtered by natural selection. This is still the dominant view in biology, and even among people who are starting to go beyond the modern synthesis, it tends to remain a background assumption. This can only be corrected by advertising the new information, especially since a lot of people are attached to the modern synthesis ideologically, as it supposedly removes teleology from biology. johnnyb

WJM, you call it an "ideological mindset". I've asked this question before and never got a clear answer: do you mean that it implies materialism? Viola Lee

It's just begging the question to say that mutations are copying errors. ET

"Why do people not just use words like genetics and evolution, etc instead of constantly using labels associated with Darwin? I don’t get it." In the same vein, why is there an Internationally Celebrated Darwin Day? ...with "dinner parties with special recipes for primordial soup and other inventive dishes, protests with school boards and other governmental bodies, workshops and symposia, distribution of information by people in ape costumes, lectures and debates, essay and art competitions, concerts, poetry readings, plays, artwork, comedy routines, re-enactments of the Scopes Trial and of the debate between Thomas H. Huxley and Bishop Samuel Wilberforce, library displays, museum exhibits, travel and educational tours, recreations of the journey of HMS Beagle, church sermons, movie nights, outreach, and nature hikes" ? Andrew asauber

The term "Darwinian" refers to the ideological mindset that serves as the foundational worldview lens through which the scientists (or other people) conduct their science or interpret the results. IOW, it's a metaphysical bias that informs expectations, theories, ideas, how to conduct experiments, what experiments are worth conducting, how to approach a process, how to evaluate and interpret information. Science doesn't operate in a metaphysical vacuum and the assumptive metaphysics matter. William J Murray

I continue to be puzzled by the use of "Darwinian" and like terms. Was it not scientists who discovered all this, and thus broadened our knowledge about how genetics works? Science is changing all the time, as we learn more, and thus certain beginning ideas, which might be simply expressed, get more complex and sophisticated. Why do people not just use words like genetics and evolution, etc instead of constantly using labels associated with Darwin? I don't get it. Viola Lee

So, in E. coli, the “SOS response” system is well-studied. In this system, when E. coli is stressed (lack of food, etc.), it tries to alter its own physiology by inducing mutations.
Does it induce mutations, or does it just not repair as many of them? In other words, they are still copying errors. From Wikipedia, Pol IV:
DNA polymerase IV is a prokaryotic polymerase that is involved in mutagenesis. It exhibits no 3??5? exonuclease (proofreading) activity and hence is error prone.
(emphasis added) Pol V:
DNA Polymerase V (Pol V) is a polymerase enzyme involved in DNA repair mechanisms in bacteria, such as Escherichia coli. ... However, Y polymerases have low sequence fidelity during replication (prone to add wrong nucleotides).
DNA Pol II is described as "high fidelity", so I'm not sure if it should be mentioned in this company. If Johnny Bartlett has any references to back his claims up, that might help clarify matters. Bob O'H

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